Major depression has been linked to recurrent stroke. It has been established that depression occurs in 10% to 27% of patients who suffer a first or recurrent stroke. In the United States, there are at least 500,000 new ischemic strokes yearly, and about 150,000 stroke survivors would develop post-stroke depression each year.
The risk of developing stroke is four times greater in those with symptoms of depression. The location of brain injury may determine the severity of post-stroke depression. Cerebrovascular changes may lead to depressive disorders. The term ‘vascular depression’ has been applied to underscore the significance of vascular pathology in the pathogenesis of depression. Depressive disorders showed a male:female ratio of about 1:2.
Carotid artery stenosis is a well known risk factor for stroke. High grade carotid artery stenosis was associated with depressive symptoms in patients with atherosclerosis. It has been observed that, depressive symptoms during early adulthood have been associated with higher levels of carotid intima-media thickening in men, but not in women. Major depression has been linked to decreased cerebrovascular reactivity, which predisposes to increased risk for stroke, in depressed patients. Although it has been known that impaired cerebral perfusion may occur in major depression, the findings have been inconclusive, and measures to relieve cerebral ischemia have not been implemented until now. A wide range of measures for cerebral perfusion augmentation in patients suffering from global or focal cerebral ischemia have been attempted for other indications. The U.S. Pat. No. 7,150,736 to Barbut describes an elongated catheter and a distally mounted expandable balloon to dilate the artery and augment blood flow. Others have used stent deployment at the site of arterial stenosis as described in U.S. Pat. No. 7,226,473 to Brar et al., and U.S. Pat. No. 6,899,730 to Rivelli, Jr. The U.S. Pat. No. 6,936,056 to Nash applies the use of atherectomy catheter to open a lumen of an occluded blood vessel. However, all these measures to augment blood flow have not been applied as a means for treatment of depression because the pathogenesis of depression and associated changes in blood flow to regions of the brain has not been elucidated.
The use of the present invention to provide a model of the cerebral hemodynamics in depression would be of use in a wide range of disease conditions for diagnosis, evaluation of treatment options, effectiveness of surgical measures, and monitoring of progress under certain medications. One object of the present invention is its application to the differential diagnosis for major depression that is of vascular origin. Depression could be a syndrome of many other brain conditions and may be related to vascular pathology. Usually, depression is diagnosed using clinical criteria according to questionnaire items in the diagnostic and statistical manual version 4 (DSM-IV). The use of the present invention to evaluate changes in the cerebral blood flow supply in association with clinical assessment using DSM-IV depression scale would provide the much needed objective diagnostic criteria for depression.
Another object of the present invention is to apply the model for assessment of treatment options. The assessment of the level of ipsilateral cerebral hypoperfusion and contralateral hyperperfusion, would determine to what extent measures need to be taken to relieve the vascular pathology. The choice of life style modification, medication or surgery could be made on the basis of established levels of cerebral blood flow velocity, in the major vessels of the artery of the circle of Willis.
A further object of the invention is the choice of the form of surgery that may be performed. There are a number of options with associated risk levels of surgery that may be used to relieve symptoms of depression, in the presence of carotid artery stenosis. The choice of stent deployment, intravascular atherectomy and endarterectomy, could be made based on the predicted level of blood flow velocity increase expected after the surgery. It has been known that psychological changes occur after open-heart surgery in some patients. A pre-surgery assessment using the model will define the risk of depression and also post-surgery changes could be evaluated and the treatment options assessed.
The present invention was used to postulate that, blood flow shunting through the anterior communicating artery (ACoA) may not be sufficient to equilibrate flow in both anterior cerebral arteries (ACAs) in depressed patients. About 60% of routine autopsy showed anomalous usually multi-channel ACoA. Anomalous ACoA is unable to equilibrate blood flow in both ACAs, creating a hemodynamic condition ipsilateral hypoperfusion and contralateral hyperperfusion. Similarly, the present invention could be applied to diagnosis of atresia, stenosis and other malformations of the ACoA that does not allow adequate blood flow through it.
Furthermore, the present invention could be used alone or in conjunction with magnetic resonance angiography to evaluate the effectiveness of measures such as balloon catheter angioplasty, stent deployment, and arterial grafts for restoration of flow through the ACoA.
Another object of the present invention is its application to the monitoring of patient's progress, while on medication with statins. Generally, statins are used for treatment of carotid plaque disease. The choice of statins in depression is based on their effect on carotid plaque, to improve cerebral perfusion and relieve symptoms of depression.
Yet another object of the present invention is its application to the monitoring of patients progress while on medication with vasodilators, such as pentoxyphylline. In general, vasodilators are used to improve cerebral perfusion. In view of the present invention, vasodilators such as pentoxyphylline, isosorbide dinitrate, and vinpocetine, could be applied in depression; and the present invention provides a means for monitoring their effects.
Another objective of the present invention is to provide a means for monitoring the effects of alternative medicine measures such as herbs, chocolates, acupuncture, light therapy, colored light therapy on cerebral perfusion, and possible effects on depressive symptoms.
A further object of the present invention is its use, for assessment of different lifestyle modification measures, including the use of diet, exercise and work/rest regimen. Assessment of routines that promote better cerebral perfusion and prevent depression would be useful to increase worker productivity.
Another object of the present invention is to assess the effect of posture on cerebral perfusion and depression. Certain postures such as head-down bed rest at −6 degrees have been associated with changes in cerebral perfusion. The latter was used to simulate the cardiovascular effects of microgravity. It may also suggest that, the model could be used to assess astronaut's risk of developing depression in-flight.
Yet another object of the present invention is to use the model, to assess the effects of measures such as lower body negative pressure (LBNP), on cerebral perfusion and the risk of depression. LBNP may be used to simulate the effects of space-flight, and could also be applied to assess the predisposition to development of cerebral hypoperfusion and hence depression. The present invention in conjunction with LBNP could be used to monitor cerebral perfusion in astronauts. Furthermore, the present invention is applicable to astronauts and divers for training assessment, before, during and after execution of mission.
Another object of the present invention is its application for assessment of the effects of hypothermia on cerebral perfusion, and its possible application to depression. Hypothermia is known to affect cerebral perfusion. However, it is not known how hypothermia may change cerebral blood flow and affect depression.
The present invention provides a method for assessment of the effects of synthetic odors and pheromones on cerebral perfusion and hence depression. As have been described in U.S. Pat. No. 6,663,571 to Njemanze P C, odors may affect cerebral mean blood flow velocity. Certain odors could be used to improve blood flow to the brain in depressed patients; the model permits the selection of these odors, to be incorporated into odorants.